Challenges to Malaria Control in the Democratic Republic of Congo and Beyond

Roughly 40% of the world's population lives in areas where they are at risk of malaria infection. In the last 15 years, the global health community has made considerable progress in reducing transmission. Despite this progress, a number of challenges to further reductions remain. This dissertation addresses three such challenges. First, I focus on the ecology that serves as a backdrop to transmission, and focus on the role agriculture may play. In doing so, I attempt to understand how agriculture affects both mosquito behavior, as well as malaria risk in under-5 children in the Democratic Republic of Congo (DRC), a country with one of the world's highest malaria burdens. My findings from this work suggest that increasing exposure to agriculture is associated with increased indoor biting among Anopheles gambiae mosquitoes, which may be the mechanism driving the observed association between agriculture and increased malaria risk. Second, I turn to address insecticide resistance, which may undermine the contributions that bed nets have in reducing transmission. One challenge in monitoring insecticide resistance is the difficulty in obtaining representative samples of mosquitoes. I make some progress in overcoming this limitation using population-based survey data collected from 2009-2016 in 21 countries across sub-Saharan Africa, and find that the effects of bed nets treated with different insecticides vary considerably, and that certain countries need to transition away from using certain insecticides. Finally, I attempt to understand how malaria spreads. To do so, I leverage genetic data on the Plasmodium falciaprum malaria parasite from 28 neutral microsatellite markers drawn from malaria-infected children living in the DRC. I consider different population genetics tools to identify whether or not the malaria parasite population can be classied into smaller subpopulations, whether or not there is evidence of isoloation-by-distance, and if there appears to be gene flow between geographically and economically proximate regions. My results indicate that the malaria parasite population in DRC is best characterized as single population with weak evidence of isolation-by-distance, with no strong evidence of gene flow or barriers to it. However, outliers were observed along DRC's border.Doctor of Philosoph

Validation of a CFD model simulating charge and discharge of a small heat storage test module based on a sodium acetate water mixture

AbstractExperimental and theoretical investigations are carried out to study the heating of a 302 x 302 x 55mm test box of steel containing a sodium acetate water mixture. A thermostatic bath has been set up to control the charging and discharging of the steel box. The charging and discharging has been investigated experimentally by measuring surface temperatures of the box as well as the internal temperature of the sodium acetate water mixture through a probe located in the center of the steel box. The temperature developments on the outer surfaces of the steel box are used as input parameters for a Computational Fluid Dynamics (CFD) model. The CFD calculated temperatures are compared to measured temperatures internally in the box to validate the CFD model. Four cases are investigated; heating the test module with the sodium acetate water mixture in solid phase from ambient temperature to 52oC; heating the module starting with the salt water mixture in liquid phase from 72oC to 95oC; heating up the module from ambient temperature with the salt water mixture in solid phase, going through melting, ending in liquid phase at 78oC/82oC; and discharging the test module from liquid phase at 82oC, going through the crystallization, ending at ambient temperature with the sodium acetate water mixture in solid phase. Comparisons have shown reasonable good agreement between experimental measurements and theoretical simulation results for the investigated scenarios

Smartphone-assisted guided self-help cognitive behavioral therapy for young people with distressing voices (SmartVoices): study protocol for a randomized controlled trial.

BACKGROUND The long-standing view that auditory verbal hallucinations (AVH) or hearing voices is a sign of schizophrenia has been challenged by research demonstrating that they lie on a continuum ranging from normal to pathological experience related to distress and need for care. Hearing voices is more prevalent in adolescence than in later life, and hearing voices during adolescence indicates a risk for severe psychopathology, functional impairments, and suicide later in life. While there is increasing evidence for the efficacy of cognitive behavioral therapy for voices (CBTv) in adults with schizophrenia, research on psychological treatments for youth with distressing voices has been scarce. The aim of the current study is to examine the efficacy of CBTv, delivered using smartphone-based Ecological Momentary Assessment Intervention (EMI) in a transdiagnostic sample of youth. METHODS This is a superiority randomized controlled trial comparing 8 weeks of CBTv-based EMI in addition to treatment as usual (TAU) versus TAU only. TAU covers both no treatment and any form of psychiatric/psychological treatment. In the EMI condition, participants will be prompted twice a day to complete an EMA survey, and receive one intervention proposal per assessment. One-hundred fifty-four youth aged 14-25 years with distressing voices will be recruited from psychiatric clinics, local private practices, internet forums, and advertisements in print and social media. Before and after the intervention phase, participants will undergo a 9-day EMA. Single-blinded assessments will be conducted at baseline (T0) and at 3-month (T1) and 6-month (T2) follow-up. The primary outcome is the distress dimension of the Auditory Hallucinations subscale of the Psychotic Symptom Rating Scales at T1. Secondary outcomes include perceived hostile intention, power, and dominance of voices, passive, aggressive, and assertive relating to voices, and negative core beliefs about the self. DISCUSSION Adolescence provides a crucial window of opportunity for early intervention for hearing voices. However, youth are notoriously reluctant help-seekers. This study offers a low-intensity psychological intervention for youth with distressing voices beyond diagnostic boundaries that, using a mobile technology approach, may match the treatment preferences of the generation of "digital natives." TRIAL REGISTRATION German Clinical Trials Register DRKS00026243. Registered on 2 September 2021

Changing spatial patterns and increasing rurality of HIV prevalence in the Democratic Republic of the Congo between 2007 and 2013

The Democratic Republic of the Congo (DRC) has one of the lowest HIV prevalence in sub-Saharan Africa, estimated at 1.1% [0.9-1.3] of adults aged 15-49 in 2013 (UNAIDS). Within the 2 million km2 country, however, there exists spatial variation in HIV prevalence, with the highest HIV prevalence observed in the large cities of Kinshasa and Lubumbashi. Globally, HIV is an increasingly rural disease, diffusing outwards from urban centers of high HIV prevalence to places where HIV was previously absent or present at very low levels. Utilizing data collected during Demographic and Health Surveillance (DHS) in 2007 and 2013 in the DRC, we sought to update the map of HIV prevalence in the DRC as well as to explore whether HIV in the DRC is an increasingly rural disease or remains confined to urban areas. Bayesian kriging and regression indicate that HIV prevalence in rural areas of the DRC is higher in 2013 than in 2007 and that increased distance to an urban area is no longer protective against HIV as it was in 2007. These findings suggest that HIV education, testing and prevention efforts need to diffuse from urban to rural areas just as HIV is doing

Government interventions and control policies to contain the first COVID-19 outbreak: An analysis of evidence

Background: The overarching aim of this study was to evaluate the effectiveness over time of government interventions and policy restrictions and the impact of determinants on spread and mortality during the first-wave of the COVID-19 pandemic, globally, regionally and by country-income level, up to 18 May 2020. Methods: We created a global database merging World Health Organization daily case reports (from 218 countries/territories) with other socio-demographic and population health measures from 21 January to 18 May 2020. A four-level government policy interventions score (low to very high) was created based on the Oxford Stringency Index. Results: Our results support the use of very high government interventions to suppress both COVID-19 spread and mortality effectively during wave one globally compared to other policy levels of control. Similar trends in virus propagation and mortality were observed in all country-income levels and specific regions. Conclusions: Rapid implementation of government interventions was needed to contain the first wave of the COVID-19 outbreak and to reduce COVID-19-related mortality.Peer ReviewedPostprint (author's final draft

Towards the development of a SARS-CoV-2 variant risk assessment tool:expert consultation on the assessment of scientific evidence on emerging variants

A systematic approach is required for the development of an evidence-based risk assessment tool to robustly estimate the risks and implications of SARS-CoV-2 variants. We conducted a survey among experts involved in technical advisory roles for WHO to capture their assessment of the robustness of different study types that provide evidence for potential changes in transmissibility, antigenicity, virulence, treatability, and detectability of SARS-CoV-2 variants. The views of 62 experts indicated that studies could be grouped on the basis of robustness and reliability for the different risk indicators mentioned. Several study types that experts scored as providing reliable evidence and that can be performed in a timely manner were identified. Although experts from different technical areas had varying responses, there was agreement on the highest and lowest scoring study types. These findings can help to prioritise, harmonise, and optimise study designs for the further development of a systematic, evidence-based, SARS-CoV-2 variant risk assessment tool.</p

Malaria surveillance in the Democratic Republic of the Congo: comparison of microscopy, PCR, and rapid diagnostic test

Malaria surveillance is critical for control efforts, but diagnostic methods frequently disagree. Here we compare microscopy, PCR, and a Rapid Diagnostic Test in 7,137 samples from children in the Democratic Republic of the Congo using Latent Class Analysis. PCR had the highest sensitivity (94.6%) and microscopy had the lowest (76.7%)

A Cross-Sectional Survey of Plasmodium falciparum pfcrt Mutant Haplotypes in the Democratic Republic of Congo

In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first-line therapy for falciparum malaria; little is known about the prevalence of molecular markers of parasite drug resistance. Across the DRC, we genotyped 166 parasites in Plasmodium falciparum chloroquine resistance transporter (pfcrt) using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73 (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine-resistant CVIET, 35 (21.1%) parasites were mixed CVMNK and CVIET, and 3 parasites were other genotypes. Ninety-two infections (55.4%) harbored the pfcrt K76T substitution that is highly correlated with chloroquine failure. The amodiaquine-resistant SVMNT haplotype was absent. Geographically, pfcrt haplotypes were not clearly clustered. Chloroquine accounted for 19.4% of antimalarial use, and amodiaquine accounted for 15.3% of antimalarial use; there were no associations between drug use and mutant haplotype prevalence. In the DRC, our molecular survey indicates that resistance to chloroquine is substantial but that resistance to amodiaquine is absent. These contrasting findings highlight the need for molecular surveillance of drug resistance to inform malaria control policies